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Leishmanicidal and cytotoxic activity from plants used in Tacana traditional medicine (Bolivia)

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Abstract

Aim of the study: To evaluate the leishmanicidal effect (IC50) and cytotoxicity (LD50) of the selected plants. To carry out bioguided studies on the active extracts. To assess the potential of Bolivian plant biodiversity associated with traditional knowledge in the discovery of alternative sources to fight leishmaniasis. Materials and methods: Seventy three ethanol extracts were prepared from 38 species by maceration and were evaluated in vitro against promastigotes of Leishmania amazonensis and L. braziliensis. Active extracts (IC50 ≤ 50 μg/mL) were fractionated by chromatography on Silica gel column and the fractions were assessed against the two Leishmania strains. The most active fractions and the crude extracts were evaluated against reference strains of L. amazonensis, L. braziliensis, L. aethiopica, two native strains (L. Lainsoni and L. braziliensis) and for cytotoxicity against HeLa cells. The chromatographic profile of the active fractions was obtained by reverse phase chromatography using HPLC. Results: From the 73 extracts, 39 extracts (53.4%) were inactive and 34 showed activity. Thirteen species were sselected for bioguided studies. The crude extracts and their 36 fractions were evaluated against two Leishmania strains. The most active fraction were tested in a panel of five leishmania strains and for cytotoxicity. The Selective Index (SI=LD50/IC50) was calculated, and were generally low. Retention time and UV spectra were recorded for the active fractions by HPLC-DAD using a reverse phase column. Profiles were very different from each other, showing the presence of different compounds. Conclusion: Bolivian traditional knowledge from the Tacanba was useful to identify plants with effect on Leishmania promastigotes. Chromatographic bioguided studies showed stronger leishmanicidal and cytotoxic activity for the medium polar fraction. HPLC analysis showed different chromatographic profiles of the active fractions.

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... The Tacana ethnic group represents almost 0.03% of the total Bolivian population, they live on the lowlands in the northern part of the La Paz Department, and has an intimate knowledge of their environment and preserve a wide use of medicinal plants, that are conserved in gardens and orts around their homes [1,2]. Currently, some 20 communities are organized through the Tacana People Counsel (CIPTA) and the Tacana Women Counsel (CIMTA), organizations that take care of conservation of their territory, natural resources and cultural aspects within their land of communal origin (TCO-Tacana1), areas in which vector transmitted diseases play an important role on health epidemiology [3,4]. ...
... All strains were cultured in Schneider's insect medium, (pH 6.2), supplemented with 10% FBS and incubated in in 96-microwell plates at 26°C. Biological assay was done as described elswhere [2]. Briefly, promastigotes in logarithmic phase of growth, at concentration of 3x10 6 parasites/mL, were exposed to samples dissolved in DMSO (1%) at different concentrations (3.1-100 μg/mL). ...
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A bioassay screening against protozoa parasites of several Tacana medicinal plants gave Hyptis brevipes (Id'ene eidhue), traditionally used as decoction for intestinal parasites, as the most active extract. In this work we did a bioguided isolation of active constituents found in leaves. Structure elucidation was carried out by NMR spectroscopy and MS spectrometry analyses. Active constituents showed differentiated activity towards Giardia lamblia, Trypanosoma cruzi, several Leishmania strains, Plasmodium falciparum and cytotoxicity against HeLa cells. Brevipolide H (1) was the less cytotoxic and best antiparasitic, while the catechol derivative (2) the most active and cytotoxic.
... Erechtites hieraciifolius is used traditionally in Venezuela (a plant decoction is used as a bath to reduce fever) and in El Salvador (a decoction is used to treat coughs) [19]. In Bolivia, the Tacana people use an oil extract of E. hieraciifolius to treat wounds and pimples [20]. An ethanol extract of E. hieraciifolius showed in vitro antileishmanial activity against promastigotes of Leishmania (Leishmania) amazonensis Lainson & Shaw and L. (Viannia) braziliensis Vianna [20]. ...
... In Bolivia, the Tacana people use an oil extract of E. hieraciifolius to treat wounds and pimples [20]. An ethanol extract of E. hieraciifolius showed in vitro antileishmanial activity against promastigotes of Leishmania (Leishmania) amazonensis Lainson & Shaw and L. (Viannia) braziliensis Vianna [20]. In North America, E. hieraciifolius was previously used to treat hemorrhages, wounds, skin diseases, and as a topical treatment for poison ivy (Toxicodendron radicans (L.) Kuntze, Anacardiaceae) and poison sumac (T. ...
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Mosquito-borne infections are a constant problem in Vietnam, and mosquito vector control is a primary approach to control these infections. Essential oils represent environmentally friendly alternatives to synthetic pesticides for mosquito control. The essential oils of two weedy species in Vietnam, Erechtites hieraciifolius and E. valerianifolius, have been obtained by hydrodistillation and analyzed by gas chromatography–mass spectrometry. The essential oils have been screened for mosquito larvicidal activity against Aedes albopictus, Ae. aegypti, and Culex quinquefasciatus. The essential oil from the aerial parts of E. hieraciifolius was rich in α-pinene (14.5%), limonene (21.4%), and caryophyllene oxide (15.1%), while E. valerianifolius essential oil was dominated by myrcene (47.8%) and α-pinene (30.2%). Both essential oils showed good larvicidal activity against Ae. albopictus (24-h LC50 10.5 and 5.8 μg/mL, respectively) and Ae. aegypti (24-h LC50 10.6 and 12.5 μg/mL, respectively). The essential oil of E. valerianifolius also showed good activity against Cx. quinquefasciatus larvae (24-h LC50 = 40.7 μg/mL). Thus, Erechtites essential oils may serve as low-cost vector control agents for mosquito-borne infections.
... In recent years, topics have been applied such as: 3-aminofurostan alkaloids from roots of Solanum paniculatum L. [16], studies on the Leishmanicidal and cytotoxic capacity of jurubeba and other plants [17], In addition, the Solanum genus plants have attracted great interest from researchers, because to the presence of bioactive compounds and antioxidant activity [18,19]. However, the authors are not aware of studies in which the influence of thermal treatments on jurubeba was evaluated, evaluating its lipid profile and antioxidant activity in vitro. ...
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The jurubeba (Solanum paniculatum L.) is an unconventional food plant, with few studies carried out so far, is a promising fruit and conservation methods are necessary to increase its shelf life. The objective was to evaluate the effect of dehydration and roasting of the fresh fruits in chemical composition, fatty acid composition, triacylglycerol profile, total phenolics, and antioxidant activity. Three treatments were obtained: fresh samples unripe; dehydrated samples subjected to drying in an air-circulation oven forced at 50 °C for 24 h; roasted samples it was used dehydrated fruits, subjecting them to the muffle at 190 °C for 20 min. We found 13 fatty acids, the percentage of them was modified by heat treatment, roasting had an increase of 9% in the sum of polyunsaturated fatty acids. The dehydration and roasting processes don’t change triacylglycerides of jurubeba while modifying their percentages, and their profile, as compared to the fresh sample. The antioxidant activity (increase of 140% and 807%) and total phenolic compounds (increase of 14% and 86%) in relation of jurubeba fresh. The PCA analysis explained 100% of the variation in sample composition, being that PC1 explained 72.7% and PC2 explained 27.3% of the data, evaluating the generated PCA graph we observed that there was no formation of groups, that is, the samples did not show similarity to each other. The jurubeba proved to be a promising fruit, encouraging future investigations into its application in new products in the food and pharmaceutical industries, which can add value to this fruit.
... R. E. Fries, and B. pleiosperma Maas), all restricted to tropical South America and east of the Andes, and only the species B. mattogrossensis has not been subjected to any phytochemical investigation. [10][11][12][13][14][15][16][17] The Neotropical genus Bocageopsis belongs to the subfamily Malmeoideae, represented in Brazil by the tribe Malmeeae. 5,18 The species with wide distribution in the Amazon region are the species B. canescens (popularly known as envireira), B. multiflora (envira or envira surucucu), and B. pleiosperma (envira preta or surueira sangue). ...
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The essential oils (EO) of three species of Bocageopsis (B. canescens, B. pleiosperma, and B. multiflora) were investigated by gas chromatography coupled to mass spectrometry (GC/MS), revealing the presence of sesquiterpenes and their derivatives. The leaves of two individuals with different stages of development of B. canescens species were analyzed, being identified in the bigger and, consequently, older individual, germacrene D (19.5%), (E)-caryophyllene (14.8%), bicyclogermacrene (9.7%), d-elemene (8.5%), and b-elemene (8.3%) as main constituents. In the younger and smaller individual, oxygenated sesquiterpenes were predominant: spathulenol (24.1%), caryophyllene oxide (9.8%), and isospathulenol (8.5%), besides the sesquiterpene (E)-caryophyllene (13,6%). The main constituents of the twig from the older individual were sesquiterpenes: α-muurolol (40.0%) and β-acorenol (16.0%). On the other hand, in the species B. multiflora, the main constituents in the EO extracted from the leaves were spathulenol (35.14%) and α-trans-bergamotene (31.23%). The main compounds in the branches were α-trans-bergamotene (25.32%), β-selinene (19.57%), and α-gurjunene (15.42%). The sesquiterpenes β-selinene (28.16%) and α-trans-bergamotene (21.92%) were predominant in the twig β-bisabolene was the main constituent in the leaves (89.64%) and twig (33.75%) of B. pleiosperma species, being also observed a significant presence of bisabolene derivative cryptomerione (25.76%) in the twig. These results represent the first report on the chemical composition of the species B. canescens from the Amazon region.
... The systemic side effects are primarily on the cardiovascular system, kidney, and liver (World Health Organization 2010). Thus, research on new natural compounds with anti-Leishmania activity is essential for the development of new therapeutic strategies with less toxicity (Adebayo et al. 2013;Demarchi et al. 2016;Ullah et al. 2016;Arévalo-Lopéz et al. 2018;Tiwari et al. 2018;Vásquez-Ocmín et al. 2018). ...
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Leishmaniasis affects millions of people worldwide, and available treatments have severe limitations. Natural and derivative products are significant sources of innovative therapeutic agents. Naphthoquinones are natural or synthetic chemical compounds with broad biological activity. This systematic review aimed to evaluate the potential anti-Leishmania activity of bioactive compounds derived from naphthoquinones in animal models. Conducted in accordance with PRISMA guidelines, two blocks of MeSH terms were assembled: group I, Leishmania OR Leishmaniasis; group II, Atovaquone OR Lapachol OR Beta lapachone OR Naphthoquinones. The search was performed on PubMed, Web of Science, SCOPUS, EMBASE, and Lilacs databases. Twenty-four articles were retrieved and submitted for quality assessment using the SYRCLE critical appraisal tool. The in vivo anti-Leishmania potential of naphthoquinones was evaluated in visceral and cutaneous leishmaniasis using several measurement parameters. Analyzed compounds varied in structure, association with reference drugs, and encapsulation using a drug delivery system. The study design, including treatment protocol, differed between studies. The findings of the studies in this systematic review indicate the anti-Leishmania potential of naphthoquinones in vivo, with different treatment regimens directed against different Leishmania species. The employed drug delivery systems improve the results concerning selectivity, distribution, and required therapeutic dose. The immunomodulatory action was shown to be beneficial to the host, favoring an adequate immune response against infection by Leishmania parasites since it favored Th1 responses. All studies presented a moderate to high risk of bias. These findings suggest that more studies are needed to assess the overall effectiveness and safety of these treatments. Graphical abstract
... Astraceae), Thalia geniculata (Fam. Marantaceae), and Ejije Bid'u leaves [54]. ...
Chapter
Leishmaniasis is a neglected tropical disease that causes severe morbidity and mortality. It has an estimated worldwide incidence of 15 million infected people and 350 million at risk, living in tropical and subtropical areas of 88 endemic countries in America, Europe, Africa, Middle East, and Asia. Current treatment of leishmaniasis relies on chemotherapy. No vaccine exists for leishmaniasis and most of the antileishmanial drugs currently in use, have disadvantages, such as severe side effects or parasite resistance. Amphotericin B and its lipid‐carrier formulations have been successfully applied, while the first line drugs were no longer effective due to drug resistance. Nevertheless, very high costs of these drugs prevent their widespread use. Alternatively, many plants and plant constituents have been used over the past years for controlling such disease. In this chapter, emphasis was made on the different plants, plant extracts as well as natural lead molecules that were proved to have antileishmanial activity.
... Various criteria have been stated in the studies to define the selective antiparasitic activities of medicinal plant extracts. For instance; selective antiparasitic activity has been reported for medicinal plant extracts when the SI value is greater than 1 by Tempone et al. [25] , greater than 2 by Arevalo-Lopez et al. [26] , and greater than 3 by Joshi et al. [27] . In addition, researchers working on synthetic derivatives recommend SI>6 as a convenient criterion [28] . ...
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It was aimed to investigate in vitro antileishmanial activities of the receptacle, bractea, and stem leaves extracts of Cynara scolymus (artichoke) against Leishmania tropica. The Leishmania isolate, isolated from a cutaneous leishmaniasis patient from Manisa province, Turkey and stored in liquid nitrogen, was identified as L. tropica (MHOM/TR/2012/CBCL-LT) by genotyping. In vitro antileishmanial activities of C. scolymus plant extracts were examined by CelltTiter-glo and hemocytometry, and cytotoxic activities by MTT. IC50 values of receptacle water (WRC), aqueous ethanol (ARC) and ethanol (ERC), bractea leaf water (WBC), aqueous ethanol (ABC) and ethanol (EBC), and stem leaf water (WSC), aqueous ethanol (ASC) and ethanol (ESC) extracts were determined as 2.45 mg/mL, 1.52 mg/mL, 1.66 mg/mL, 3.45 mg/mL, 1.46 mg/mL and 0.58 mg/mL, 0.24 mg/mL, 0.21 mg/mL and 0.08 mg/mL, respectively. When these results are compared with the drug-free control group, it was determined that stem leaf aqueous ethanol (SI: 7.98), ethanol (SI: 4.96) and water (SI: 2.71) extracts with the highest selectivity index (SI) values showed antileishmanial activity (P<0.05). Extracts of C. scolymus did not show cytotoxic activity except for WBC, WRC and ARC. In conclusion, the data presented in the current study indicated that C. scolymus stem leaf extracts (ESC, ASC and WSC) present eff ective antileishmanial activity. Future studies could focus on the identification and purification of the antileishmanial compounds within these extracts for analysis of their in vivo antileishmanial activity.
... In the community of Buena Vista, Bolivia, thirty-eight plants have been used to treat skin problems, and eight of them were recommended by Tacana medicine for the treatment of leishmaniasis (Arévalo-Lopéz et al., 2018). Extracts were produced with all these plants, and the leishmanicidal activity assayed on promastigote forms of L. (L.) amazonensis and L. (V.) braziliensis. ...
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Leishmaniasis is a neglected tropical disease that affects people living in tropical and subtropical areas of the world. There are few therapeutic options for treating this infectious disease, and available drugs induce severe side effects in patients. Different communities have limited access to hospital facilities, as well as classical treatment of leishmaniasis; therefore, they use local natural products as alternative medicines to treat this infectious disease. The present work performed a bibliographic survey worldwide to record plants used by traditional communities to treat leishmaniasis, as well as the uses and peculiarities associated with each plant, which can guide future studies regarding the characterization of new drugs to treat leishmaniasis. A bibliographic survey performed in the PubMed and Scopus databases retrieved 294 articles related to traditional knowledge, medicinal plants and leishmaniasis; however, only 20 were selected based on the traditional use of plants to treat leishmaniasis. Considering such studies, 378 quotes referring to 292 plants (216 species and 76 genera) that have been used to treat leishmaniasis were recorded, which could be grouped into 89 different families. A broad discussion has been presented regarding the most frequent families, including Fabaceae (27 quotes), Araceae (23), Solanaceae and Asteraceae (22 each). Among the available data in the 378 quotes, it was observed that the parts of the plants most frequently used in local medicine were leaves (42.3% of recipes), applied topically (74.6%) and fresh poultices (17.2%). The contribution of Latin America to studies enrolling ethnopharmacological indications to treat leishmaniasis was evident. Of the 292 plants registered, 79 were tested against Leishmania sp. Future studies on leishmanicidal activity could be guided by the 292 plants presented in this study, mainly the five species Carica papaya L. (Caricaceae), Cedrela odorata L. (Meliaceae), Copaifera paupera (Herzog) Dwyer (Fabaceae), Musa × paradisiaca L. (Musaceae), and Nicotiana tabacum L. (Solanaceae), since they are the most frequently cited in articles and by traditional communities.
... Various criteria have been stated in the studies to define the selective antiparasitic activities of medicinal plant extracts. For instance; selective antiparasitic activity has been reported for medicinal plant extracts when the SI value is greater than 1 by Tempone et al. [25] , greater than 2 by Arevalo-Lopez et al. [26] , and greater than 3 by Joshi et al. [27] . In addition, researchers working on synthetic derivatives recommend SI>6 as a convenient criterion [28] . ...
Full-text available
Article
It was aimed to investigate in vitro antileishmanial activities of the receptacle, bractea, and stem leaves extracts of Cynara scolymus (artichoke) against Leishmania tropica. The Leishmania isolate, isolated from a cutaneous leishmaniasis patient from Manisa province, Turkey and stored in liquid nitrogen, was identified as L. tropica (MHOM/TR/2012/CBCL-LT) by genotyping. In vitro antileishmanial activities of C. scolymus plant extracts were examined by CelltTiter-glo and hemocytometry, and cytotoxic activities by MTT. IC50 values of receptacle water (WRC), aqueous ethanol (ARC) and ethanol (ERC), bractea leaf water (WBC), aqueous ethanol (ABC) and ethanol (EBC), and stem leaf water (WSC), aqueous ethanol (ASC) and ethanol (ESC) extracts were determined as 2.45 mg/mL, 1.52 mg/mL, 1.66 mg/mL, 3.45 mg/mL, 1.46 mg/mL and 0.58 mg/mL, 0.24 mg/mL, 0.21 mg/mL and 0.08 mg/mL, respectively. When these results are compared with the drug-free control group, it was determined that stem leaf aqueous ethanol (SI: 7.98), ethanol (SI: 4.96) and water (SI: 2.71) extracts with the highest selectivity index (SI) values showed antileishmanial activity (P
... The treatment consists of preparing an infusion of the bark boiled in water, which was drunk daily and the procedure was widespread among the Tacanas. During an ongoing screening of Bolivian plants for metabolites with antiparasitic activities [4], an ethanol extract of the bark of T. adolfi was found to possess antileishmanial properties. As this species is poorly investigated for contents of secondary metabolites, a phytochemical study including the testing of isolated metabolites for antileishmanial activities, motivated the examination presented here. ...
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The fractionation of an ethanol extract of the bark of Trichilia adolfi yielded four novel limonoids (trichilinones A-D, 1-4), with five fused rings and related to the hortiolide-type limonoids. Starting with an ε-lactone, which is α,β-unsaturated in trichilinones A and D (1 and 4), attached to a tetrahydrofuran ring that is connected to an unusual bicyclo [5.1.0] hexane system, joined with a cyclopentanone with a 3-furanyl substituent [(2-oxo)-furan-(5H)-3-yl in trichilinone D (4)], the four compounds isolated display a new 7/5/3/5/5 limonoid ring system. Their structures were established based on extensive analysis of NMR spectroscopic data. As the crude extract possessed anti-leishmanial properties, the compounds were assayed for cytotoxic and anti-parasitic activities in vitro in murine macrophages cells (Raw 264.7) and leishmania promastigotes (L. amazoniensis and L. braziliensis), respectively. The compounds showed moderate cytotoxicity (approximately 70 μg/mL), but are not responsible for the leishmanicidal effect of the extract.
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Leishmaniasis is one of the most neglected tropical diseases that present areal public health problems worldwide. Chemotherapy has several limitations such as toxic side effects, high costs, frequent relapses, the development of resistance, and the requirement for long-term treatment. Effective vaccines or drugs to prevent or cure the disease are not available yet. Therefore, it is important to dissect antileishmanial molecules that present selective efficacy and tolerable safety. Several studies revealed the antileishmanial activity of medicinal plants. Several organic extracts/essential oils and isolated natural compounds have been tested for their antileishmanial activities. Therefore, the aim of this review is to update and summarize the investigations that have been undertaken on the antileishmanial activity of medicinal plants and natural compounds derived, rom plants from January 2015 to December 2021. In this review, 94 plant species distributed in 39 families have been identified with antileishmanial activities. The leaves were the most commonly used plant part (49.5%) followed by stem bark, root, and whole plant (21.9%, 6.6%, and 5.4%, respectively). Other plant parts contributed less (<5%). The activity was reported against amastigotes and/or promastigotes of different species (L. infantum, L. tropica, L. major, L. amazonensis, L. aethiopica, L. donovani, L. braziliensis, L. panamensis, L. guyanensis, and L. mexicana). Most studies (84.2%) were carried out in vitro, and the others (15.8%) were performed in vivo. The IC50 values of 103 plant extracts determined in vitro were in a range of 0.88 µg/mL (polar fraction of dichloromethane extract of Boswellia serrata) to 98 µg/mL (petroleum ether extract of Murraya koenigii). Among the 15 plant extracts studied in vivo, the hydroalcoholic leaf extract of Solanum havanense reduced parasites by 93.6% in cutaneous leishmaniasis. Voacamine extracted from Tabernaemontana divaricata reduced hepatic parasitism by ≈30 times and splenic parasitism by ≈15 times in visceral leishmaniasis. Regarding cytotoxicity, 32.4% of the tested plant extracts against various Leishmania species have a selectivity index higher than 10. For isolated compounds, 49 natural compounds have been reported with anti-Leishmania activities against amastigotes and/or promastigotes of different species (L. infantum, L. major, L. amazonensis, L. donovani and L. braziliensis). The IC50 values were in a range of 0.2 µg/mL (colchicoside against promastigotes of L. major) to 42.4 µg/mL (dehydrodieuginol against promastigotes of L. amazonensis). In conclusion, there are numerous medicinal plants and natural compounds with strong effects (IC50 < 100 µg/mL) against different Leishmania species under in vitro and in vivo conditions with good selectivity indices (SI > 10). These plants and compounds may be promising sources for the development of new drugs against leishmaniasis and should be investigated in randomized clinical trials.
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Evaluation of the leishmanicidal activity of different mixtures of β-caryophyllene oxide and lupenone against Old and New World Leishmania spp. showed that both the pure β-caryophyllene oxide and the 1:4 mixture of lupenone and β-caryophyllene oxide are similarly active against promastigotes of L. amazonensis, L. braziliensis, L. mexicana, L. tropica, and L. aethiopica, with IC50 values ranging from 14 to 39.3 μg/ml, and reduce the infectivity of macrophages by L. mexicana and L. tropica. However, the 1:4 mixture of lupenone and β-caryophyllene oxide showed a better selectivity index than the pure sesquiterpene and increased production of NO, H2O2, and cytokines; these results suggest that the 1:4 mixture of terpenoids has both leishmanicidal activity and an immunomodulator effect, without affecting cell viability.Graphical abstract
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The goal of this study was to evaluate the anesthetic potential of an ethanolic extract of Hyptis mutabilis and its effects on behavior, biochemistry, ionic balance, and oxidative stress biomarkers of silver catfish (Rhamdia quelen) after 24-h exposure. Additionally, its chemical composition was determined by high performance liquid chromatography coupled with a diode array detector and tandem mass spectrometry (HPLC-DAD-MS/MS) to identify its bioactive compounds. The concentration range of 50–500 mg L⁻¹ induced only partial loss of equilibrium (14–2 min) in fish. There was quick recovery (about 5 min) with 50 and 100 mg L⁻¹, while not all animals recovered within 30 min exposure to the higher concentrations. Fish exposed to 100 mg L⁻¹ maintained a sedative level during the long-term experiment. There were lower plasma glucose and lactate levels in fish exposed to the extract compared with the control group (water). There were net Na⁺ and K⁺ influxes after exposure to the extract, while Cl⁻ effluxes were observed in all groups (treated or not). Ammonia excretion decreased in animals exposed to extract, and creatinine elimination did not change. Fish exposed to 100 mg L⁻¹ showed higher catalase and glutathione S-transferase activities in the kidney, while glutathione-dependent peroxidase activity increased in the liver. Lipid peroxidation in the kidney did not differ among experimental groups, while there were lower levels in the liver of juveniles exposed to the extract. There was no mortality or side effects in any of the experiments. Rosmarinic acid (53.76 ± 0.13 mg g⁻¹ extract) and rutin (5.75 ± 0.28 mg g⁻¹ extract) were identified in the extract based on standards. In conclusion, the ethanolic extract of H. mutabilis is a promising fish sedative at 100 mg L⁻¹. Its use for long-term exposure showed a good safety margin and ability to prevent stress. Hence, it can be proposed for use in the transport of aquatic animals.
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Ethnopharmacological relevance The subtribe Hyptidinae contains approximately 400 accepted species distributed in 19 genera (Hyptis, Eriope, Condea, Cantinoa, Mesosphaerum, Cyanocephalus, Hypenia, Hyptidendron, Oocephalus, Medusantha, Gymneia, Marsypianthes, Leptohyptis, Martianthus, Asterohyptis, Eplingiella, Physominthe, Eriopidion and Rhaphiodon). This is the Lamiaceae clade with the largest number of species in Brazil and high rates of endemism. Some species have been used in different parts of the world mainly as insecticides/pest repellents, wound healing and pain-relief agents, as well as for the treatment of respiratory and gastrointestinal disorders. Aim of the review This review aims to discuss the current status concerning the taxonomy, ethnobotanical uses, phytochemistry and biological properties of species which compose the subtribe Hyptidinae. Materials and methods The available information was collected from scientific databases (ScienceDirect, Pubmed, Web of Science, Scopus, Google Scholar, ChemSpider, SciFinder ACS Publications, Wiley Online Library), as well as other literature sources (e.g. books, theses). Results The phytochemical investigations of plants of this subtribe have led to the identification of almost 300 chemical constituents of different classes such as diterpenes, triterpenes, lignans, α-pyrones, flavonoids, phenolic acids and monoterpenes and sesquiterpenes, as components of essential oils. Extracts, essential oils and isolated compounds showed a series of biological activities such as insecticide/repellent, antimicrobial and antinociceptive, justifying some of the popular uses of the plants. In addition, a very relevant fact is that several species produce podophyllotoxin and related lignans. Conclusion Several species of Hyptidinae are used in folk medicine for treating many diseases but only a small fraction of the species has been explored and most of the traditional uses have not been validated by current investigations. In addition, the species of the subtribe appears to be very promising, as alternative sources of podophyllotoxin-like lignans which are the lead compounds for the semi-synthesis of teniposide and etoposide, important antineoplastic agents. Thus, there is a wide-open door for future studies, both to support the popular uses of the plants and to find new biologically active compounds in this large number of species not yet explored.
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Parasitoses are very common throughout the world, generating serious consequences for public health. Leishmaniosis and giardiasis are examples of fairly recurrent, but neglected diseases. Several higher plants have demonstrated promising activity against the parasites. The aim of this study was to evaluate the biological activity of extracts, fractions and isolated compounds from the leaves and stems of two Brazilian plants: Eugenia mattosii and Marlierea eugeniopsoides (Myrtaceae) against Leishmania and Giardia. XTT and the fluorimetric method were used to for this evaluation, respectively. Cytotoxicity was evaluated against HeLa cells. The results demonstrated that chloroform fractions of E. matosii and pinostrobin presented the most pronounced antiparasitic activity, with the CLF-stems being the most effective against Leishmania amazonensis and Leishmania braziliensis. Pinostrobin also presented activity against G. lamblia. Therefore, E. mattosii stems and pinostrobin may be considered possible targets for the continuity of studies against other parasites.
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Ethnopharmacological relevance: Cedrela serrata Royle (C. serrata) is a medicinal plant not only used for constructions but also an important conventional medicine for the treatment of various diseases such as; diabetes, jaundice, liver diseases, diarrhea, fever, chronic infantile dysentery, intestinal worms, hypertension, skin and blood diseases. Aims: This review article documents and critically assesses, for the first time; up to date categorized information about C. serrata including its reported pharmacological activities, cultural uses, active compounds, and botanical description. Materials and method: s: All provided information about C. serrata was collected using the electronic databases (e.g. Google Scholar, Web of Science, Scopus, PubMed, Science Direct and Springer Link), books (e.g. Trees of Pakistan and Herbalism, Phytochemistry, and Ethnopharmacology) and thesis. Results: Qualitative and quantitative phytochemical studies on C. serrata revealed the presence of important chemical constituents such as; flavonoids, phenolic acids, alkaloids, saponins, tannins, and cardiac glycosides. The phytochemicals showed various in vitro activities like antioxidant, anti-infective, antiglycation, cytotoxic activities. Major areas of research conducted on C. serrata are its antioxidant and anti-infective activities. Few historical uses of C. serrata are supported by modern in vitro pharmacological studies such as; antidiarrheal, antidiabetic, and leishmanicidal activity. Conclusion: There were convincing evidence in in vitro studies supporting C. serrata antioxidant, anti-infective, anti-diabetic, anti-glycating, and cytotoxic activities. Nevertheless, all reported pharmacological activities were carried out in vitro and a gap in research i.e. preclinical and clinical investigation still exists. The authors emphasize the need for future in-depth research and clinical trials to investigate C. serrata pharmacological activity, clinical efficacy and safety. The potential chemical compounds with suggestive classes may need to be isolated and pharmacological activities must be established for these compounds. The plant has very limited information about pharmacological activities and the data available for supportive cultural uses needs proper validation.
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Context: Previous reports informed about the species-specific condition of plant phenolic profiles and the association between phenolic composition and plant antioxidant properties. The species-specific condition of phenolic patterns offers the opportunity to develop chemical quality markers for plants used in traditional medicine. However, changes in phenolic composition can occur during plant growth. Physalis angulata is an important medicinal plant for which the age-related variation of phenolic composition and antioxidant properties is unknown. Aims: To assess the phenolic composition and antioxidant properties of above- and under-ground parts of P. angulata at four growth stages and evaluate their potential as chemical quality indicators. Methods: A method of HPLC-DAD was used to assess the phenolic profiles. Anti-radical potential, total antioxidant capacity and iron reducing power were evaluated by spectrometric methods. Sample distinctiveness was determined by cluster analyses. Results: The HPLC-DAD analysis revealed 21 phenolic compounds, which were accumulated in a tissue- and age-specific manner. On the contrary, a clear distinctiveness between phenolic contents and antioxidant properties of samples was not observed. Mature flowers highlighted for its total phenolic content (6.50 mg/g fresh tissue) and total antioxidant capacity (416.1 μg/mL). Young leaves were outstanding for its flavonoid content (37.86 μg/g fresh tissue) and reducing power (A700nm = 4.04). Immature calyces were worthy for its phenolic acid concentration (1.28 μg/g fresh tissue) and its free radical scavenging activity (EC50 = 0.12 mg/mL). Conclusions: Phenolic profiles represent reliable chemical quality indicators for determining plant age, tissular origin, authenticity, and adulteration of herbal preparations of P. angulata.
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The genus Vitex, which belongs to the Verbenaceae family, includes approximately 250 species. Some species of the genus Vitex have traditionally been used for the treatment of headaches, ophthalmodynia, coughs, asthma, premenopausal syndrome, etc. Chemical investigations indicate that the characteristic constituents of the genus Vitex are terpenes, and 210 of these compounds, including monoterpenoids, sesquiterpenoids, diterpenoids and triterpenoids, have been obtained from 12 species. Pharmacological studies had shown that these terpenes possess anti-inflammatory, antitumor, antibacterial, antioxidant activities, and so on. In this paper, the identity of these terpenes and their pharmacological effects are reviewed, which can provide references for further research regarding the chemistry and utilization of the Vitex species.
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Background Nepal is very rich in biodiversity, and no extensive effort has yet been carried out to screen plants that are used by traditional healers against parasitic diseases. The aim of this study was to evaluate the in vitro antileishmanial and antimalarial activity of crude methanolic or ethanolic extracts of 29 plant species that are currently used by local people of Nepal for treating different ailments. Methods Crude extracts of leaves, twigs, aerial parts, and/or roots of the selected plants were evaluated for in vitro inhibitory activity against intracellular amastigotes of Leishmania infantum and against erythrocytic stages of Plasmodium falciparum. To determine the selectivity index (SI), cytotoxicity was assessed on MRC-5 cells in parallel. Results Three plant species, namely Phragmites vallatoria and Ampelocissus tomentosa, for which no antiprotozoal activity has previously been reported, and Terminalia chebula revealed antiprotozoal activity. The extract of A. tomentosa exhibited moderate activity against L. infantum with an inhibitory concentration 50% (IC50) of 13.2 ± 4.3 µg/ml and SI >3, while T. chebula exhibited fairly good antiplasmodial activity with IC50 values of 4.5 ± 2.4 µg/ml and SI values >5. Conclusion In countries like Nepal, where the current health system is unable to combat the burden of endemic parasitic diseases, evaluation of local plants as a potential source of the drug can help in expanding the treatment options. The extent of untapped resources available in these countries provides an opportunity for future bioprospecting.
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The interest in phytopharmaceutical products and herbal medicines has been a trend in recent years and this approach may be useful as basis for developing new treatment against leishmaniasis. In this review, we discuss the perspectives of leishmaniasis treatment based on natural products and phytotherapy and compare it to the advantages and disadvantages of using the current drugs of first- and second-choice against leishmaniasis. The reports gathered herein reinforce the leishmanicidal effects of medicinal plants and its derivatives, such as Kalanchoe pinnata, Plumbago scandens, Physalis angulata, Piper aduncum, Peschiera (Tabernaemontana) australis, Phyllanthus amarus, and Artemisia annua, and indicates their use as possible alternative or complementary treatments against leishmaniasis. The data presented here support the use of medicinal plants as safe and inexpensive treatments for leishmaniasis.
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BACKGROUND: Leishmaniasis is an infectious disease caused by various species of the protozoan parasites of the Leishmania genus and transmitted by phlebotomine sandflies. The protozoa multiply in phagocytic cells, mainly macrophages, which play an important role defending the organism from pathogens. The most effective treatment for leishmaniasis is the chemotherapy and besides the high cost, these drugs are toxic and require a long period of treatment. Currently, some herbal products are considered an important alternative source of a new leishmanicidal agent, which includes the plant Physalis angulata, . We evaluated effects of an aqueous extract from roots of Physalis angulata (AEPa) on Leishmania proliferation, morphology and also determined whether physalins were present in the extract contributing to the knowledge of its pharmacological efficacy. METHODS: Morphological alterations were determined by light microscopy, transmission and scanning electron microscopy. Host cell viability was evaluated by MTT, and propidium iodide. AEPa were submitted in full HRESITOF analysis. RESULTS: AEPa promoted a dose-dependent reduction on promastigotes (IC50 = 39.5 μg/mL ± 5.1) and amastigotes (IC50 = 43.4 μg/mL ± 10.1) growth. This growth inhibition was associated with several morphological alterations observed in promastigote forms. No cytotoxic effect in mammalian cells was detected (IC50 > 4000 μg/mL). Furthemore, the presence of physalins A, B, D, E, F, G and H were described, for the first time, in the P. angulata root. CONCLUSIONS: Results demonstrate that AEPa effectively promotes antileishmanial activity with several important morphological alterations and has no cytotoxic effects on host cells.
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Leishmaniasis is a complex of diseases caused by Leishmania protozoa which treatment is restricted to a limited number of drugs that exhibit high toxicity, collateral effects and are often costly. There are a variety of tropical plants distributed in Brazil, and for many poor people the therapy for several diseases is based mainly on the use of traditional herbal remedies. In this work, the cytotoxic activity of 17 plant methanol extracts was evaluated on several Leishmania species and murine macrophages. Among them, the extract of Casearia sylvestris, Piptocarpha macropoda, Trembleya parviflora, Samanea tubulosa and Plectranthus neochilus showed a promissing leishmanicidal activity, exhibiting IC50 values below of 20 µg/mL against at least one species of Leishmania. Casearia sylvestris showed the most expressive activity against all promastigote forms of Leishmania species (IC50 values of 5.4 µg/mL, 5.0 µg/mL, 8.5 µg/mL and 7.7 µg/mL for L. amazonensis, L. braziliensis, L. chagasi and L. major, respectively), being more effective than the reference drug miltefosine. In spite of the cytotoxic effect on macrophages (CC50 value of 5.2 µg/mL), C. sylvestris exhibited a strong inhibition against intracellular amastigotes of L. braziliensis (IC50 value of 1.3 µg/mL). Further studies, including bio-guided fractionation will be conducted to identify the active compounds.
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Based on an ethnobotanical survey, 41 Guinean plant species widely used in the traditional treatment of fever and/or malaria were collected. From these, 74 polar and apolar extracts were prepared and tested for their in vitro antiprotozoal activity along with their cytotoxicity on MRC-5 cells. A potent activity (IC50 < 5 µg/mL) was observed for Terminalia albida, Vismia guineensis, Spondias mombin, and Pavetta crassipes against Plasmodium falciparum; for Pavetta crassipes, Vismia guineensis, Guiera senegalensis, Spondias mombin, Terminalia macroptera, and Combretum glutinosum against Trypanosoma brucei brucei; for Bridelia ferruginea, G. senegalensis, V. guineensis, P. crassipes, and C. glutinosum against Trypanosoma cruzi. Only the extract of Tetracera alnifolia showed a good activity (IC50 8.1 µg/mL) against Leishmania infantum. The selectivity index of the active samples varied from 0.08 to > 100. These results may validate at least in part the traditional use of some of the plant species.
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Physalis angulata L., Solanaceae, is an annual herb commonly used in popular medicine in many tropical and subtropical countries. P. angulata extracts contain a variety of substances, but little is known about their pharmacological activities. In this work we investigated the in vitro antileishmanial activity of seco-steroids (physalins) purified from P. angulata. Addition of physalins B, F, and G caused a concentration-dependent inhibition in the growth of L. amazonensis promastigotes, being the IC50 values were 6.8, 1.4, and 9.2 μM, respectively. Physalin D was less active and had an IC50 value of 30.5 μM. Physalins were also active in cultures of other Leishmania species (L. major, L. braziliensis, and L. chagasi). Our results demonstrate the potent antileishmanial activity of physalins in cultures of Leishmania species of the New and Old Worlds and suggest the therapeutic potential of these seco-steroids in leishmaniasis.
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Vitex cymosa Bertero ex Spreng., Lamiaceae, is found in Central and Amazon regions of Brazil, where it is popularly used as antirheumatic. Extracts from the leaves of V. cymosa were tested in analgesia models such as abdominal contortions induced by acetic acid and formalin to test peripheral analgesia; as well as the tail flick and hot plate models, to test spinal and supraspinal analgesia. A significant reduction was observed in the number of contortions with all extracts and in all doses. In the formalin model, a reduction in the second phase (inflammatory) was observed with all extracts, whereas only the n-butanol extract was able to act in the first, neurogenic, phase. In the tail flick model, all extracts increased latency time. Naloxone treatment reverted analgesic effect of all extracts with the exception of the dichloromethane one. All extracts developed peripheral and central analgesic activity. In the hot plate model no antinociceptive effect was observed for all tested extracts. All these results taken together suggest that V. cymosa leaf extracts were able to promote peripheral and central antinociceptive activity mediated by the opioid system. Twenty three substances were isolated and identified in the extracts and include flavonoids (C-glucosyl flavones, flavones and flavonols), triterpene acids from ursane and oleanane types, iridoids (free and glucosides), as well as simple phenols.
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A high performance liquid chromatography coupled with photodiode array detection method was developed for the identification and quantification of p-hydroxy benzoic acid and agnuside in the extracts of Vitex negundo and Vitex trifolia. The separation was achieved using acetonitrile and O-phosphoric acid–water (0.5%, v/v) as the mobile phase in an isocratic elution mode. Mean retention times of standard p-hydroxy benzoic acid and agnuside were 6.14 and 11.90 min respectively. The developed method was validated as per the ICH guidelines for limit of detection, limit of quantification, linearity, accuracy and precision. Good linearity (r2≥0.999) was observed for both the compounds in wide concentration range. Relative standard deviation values for intra-day and inter-day precision studies were less than 2%. The analytical recoveries of p-hydroxy benzoic acid and agnuside by the developed HPLC method were 93.07% and 106.11% respectively. Two compounds were identified and quantified in leaves and bar extracts of V. negundo and V. trifolia using the developed HPLC method.
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Three new labdane-derived diterpenes, dulcinodal (1), dulcinodiol (2), and scopadiol decanoate (3) were isolated from the aerial parts of Scoparia dulcis. The structures were determined by extensive NMR studies and comparison of their spectral data with related compounds.
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In vitro leishmanicidal effect of Stachytarpheta cayennensis (Rich.) Vahl (Verbenaceae)". Leishmanicidal activity of the hydroalcoholic extract of Stachytarpheta cayennensis, species that is usually employed in ulcers caused by Leishmania, was evaluated in vitro using Leishmania braziliensis and L. amazonensis promastigotes forms. The hydroalcoholic extract was prepared from dried leaves and used in L. amazonensis and L. braziliensis promastigotes cultures at concentrations of 500 to 32.5 ó g/mL. After 24 hours the promastigotes forms were quantifi ed and the IC 50 was calculated. The cytotoxicity of the extract was evaluated using peritoneal macrophages. The extract presented a dose and specie-dependent leishmanicidal effect to Leishmania promastigotes, mainly to the L. braziliensis ones. The cytotoxic effect was not observed in macrophage cultures. In conclusion, the hydroalcoholic extract of S. cayennensis inhibits the growing of Leishmania promastigotes forms in vitro accounting for the folk use of this vegetal in skin ulcers caused by Leishmania.
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The leishmaniasis and Chagas diseases constitute a serious public health problem worldwide with few and ineffective treatment options. The search for new antiparasitic candidates at the initial steps of drug discovery and development is still necessary. The synthesis of 22 de novo synthetized N,N'-dihetaryl-alkyldiamine derivatives and in vitro antiparasitic activity were evaluated for the first time against intracellular and extracellular forms of Leishmania (Leishmania) infantum, L. (Viannia) panamensis, L. (Leishmania) amazonensis, and Trypanosoma cruzi. Additionally, the toxicity on mammalian cells was determined. Some of these substituted N,N'-diamines (25-35 % of the tested compounds) showed interesting results against free-living forms of parasites with activities at the inhibitory concentration (IC 50 ) level of 1.96 to 28.83 μM for L. (L.) infantum promastigotes and IC50 of 0.02 to 5.31 μM for T. cruzi epimastigotes. No activity at the IC50 level on intracellular amastigotes of T. cruzi was observed. However, N (1),N (2)-dibenzylethane-1,2-diamine 5a revealed an important activity against the intracellular amastigotes of L. infantum (IC50 25.42 μM ±0.33) and L. panamensis (IC50 58.20 μM ±3.23), while their analogue N(1),N(4) -dibenzylbutane-1,4-diamine 5c resulted in activity only against L. panamensis (IC50 11.19 μM ±0.20) without toxicity on Vero and THP-1 mammalian cells. The active compounds against intracellular parasites with low toxicity in mammalian cells may be considered for future studies in experimental models.
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The 20th Anniversary of a Learned Society is a momentous event in its af­ fairs, and it is fitting that, in the Appendix to the Proceedings of the 20th An­ niversary Meeting, the history of the Society for Drug Research is outlined. The aim of the Society, to encourage an interdisciplinary approach and to act as an organisation freed from any specific scientific branch of knowledge, was achieved and is exemplified by the publication of these proceedings of the Anniversary Meeting held at the Pharmaceutical Society of Great Britain. In only two other cases have the Society's proceedings been published, main­ taining the original decision and policy to allow membership to enjoy com­ munications from those who may not have agreed to speak had publication been mandatory. The papers presented at the Anniversary Meeting covered a wide range of scientific disciplines, and it is fitting that work of such calibre should have been published under the able editorship of Stuart and Bryan Walker. They should prove invaluable to those who are interested in Drug Research.
Article
Ethnopharmacological relevance: In the Peruvian Amazon, the use of medicinal plants is a common practice. However, there is few documented information about the practical aspects of their use and few scientific validation. The starting point for this work was a set of interviews of people living in rural communities from the Peruvian Amazon about their uses of plants. Protozoan diseases are a public health issue in the Amazonian communities, who partly cope with it by using traditional remedies. Validation of these traditional practices contributes to public health care efficiency and may help identify new antiprotozoal compounds. Aims of study: to inventory and validate the use of medicinal plants by rural people of Loreto region. Materials and methods: Rural mestizos were interviewed about traditional medication of parasite infections with medicinal plants. Ethnopharmacological surveys were undertaken in two villages along Iquitos-Nauta road (Loreto region, Peru), namely 13 de Febrero and El Dorado communities. Forty-six plants were collected according to their traditional use for the treatment of parasitic diseases, 50 ethanolic extracts (different parts for some of the plants) were tested in vitro on Plasmodium falciparum (3D7 sensitive strain and W2 chloroquine resistant strain), Leishmania donovani LV9 strain and Trypanosoma brucei gambiense. Cytotoxic assessment (HUVEC cells) of the active extracts was performed. Two of the most active plants were submitted to preliminary bioguided fractionation to ascertain and explore their activities. Results: From the initial plants list, 10 were found to be active on P. falciparum, 15 on L. donovani and 2 on the three parasites. The ethanolic extract from Costus curvibracteatus (Costaceae) leaves and Grias neuberthii (Lecythidaceae) bark showed strong in vitro activity on P. falciparum (sensitive and resistant strain) and L. donovani and moderate activity on T. brucei gambiense. Conclusions: The Amazonian forest communities in Peru represents a source of knowledge on the use of medicinal plants. In this work, several extracts with antiprotozoal activity were identified. This work contributes to validate some traditional uses and opens subsequent investigations on active compounds isolation and identification.
Article
A new withanolide (1), physagulide P, together with five known withanolides (2–6), was isolated from the aerial parts of Physalis angulata L. The structure of new compound was elucidated on the basis of extensive spectroscopic techniques, including 1D, 2D NMR and HRESIMS. The activity screening indicated that compound 1 showed significant cytotoxicities against the human osteosarcoma cell line MG-63, HepG-2 hepatoma cells and breast cancer cells MDA-MB-231 with the IC50 value of 3.50, 4.22 and 15.74 μM.
Article
Isolation of compounds from methanol extract from the leaves of Adiantum latifolium Lam. had been conducted by using radial chromatography and thin layer chromatography (TLC) techniques. Their structures were elucidated by ultraviolet-visible (UV), infrared (IR), nuclear magnetic resonance (NMR) and mass spectroscopy (MS) and by comparison with the previous literatures. Four steroids compound were isolated namely the Stigmast-4-en-3-one (1), Stigmasta-4,22-dien-3-on (2), Stigmasterol (3) and β-Sitosterol (4). © 2017, Malaysian Society of Analytical Sciences. All rights reserved.
Article
The investigation for stems and leaves of Physalis angulata led to the isolation of twelve new labdane-type diterpenoid glycosides, physangulatosides A–L (1–12). Their structures were established on the basis of NMR, IR, UV, and HRESIMS spectra. All isolated compounds were assayed for inhibitory activities against LPS-induced NO production in RAW 264.7 macrophages. Compounds 6–10 displayed inhibitory effects against NO production with IC50 values of 15.9 ± 1.0–60.7 ± 3.8 μM. Herein, a plausible biosynthetic pathway for compounds 1–12 was also discussed.
Article
Ethnopharmacology relevance: Stachytarpheta cayennensis is a plant that is traditionally used to treat tegumentary leishmaniasis and as an anti-inflammatory agent. Aim of the study: This study aimed to evaluate the action of S. cayennensis extracts on the Leishmania (Leishmania) amazonensis arginase enzyme. Materials and methods: S. cayennensis was collected from the Brazilian Amazon region. Aqueous extracts were fractionated with n-butanol. The leishmanicidal effects of the n-butanolic fraction (BUF) were evaluated in L. (L.) amazonensis promastigotes and amastigotes. BUF was tested against recombinant arginase from both L. (L.) amazonensis and macrophage arginase. Promastigote cultures and infected macrophage cultures were supplemented with l-ornithine to verify arginase inhibition. NMR analysis was used to identify the major components of BUF. Results: BUF showed an EC50 of 51 and 32µg/mL against promastigotes and amastigotes of L. (L.) amazonensis, respectively. BUF contains a mixture of verbascoside and isoverbascoside (7:3 ratio) and is a potent L. (L.) amazonensis arginase inhibitor (IC50 = 1.2µg/mL), while macrophage arginase was weakly inhibited (IC50 > 1000µg/mL). The inhibition of arginase by BUF in promastigotes and amastigotes could be demonstrated by culture media supplementation with l-ornithine, a product of the hydrolysis of l-arginine by arginase. Conclusions: Leishmanicidal effects of the S. cayennensis BUF fraction on L. (L.) amazonensis are associated with selective parasite arginase inhibition.
Article
In this work, microwave‐assisted extraction (MAE) technique was developed for the extraction of total polyphenols from Physalis angulata. Several parameters of the MAE procedure (ethanol concentration, irradiation power, extraction time and liquid‐to‐solid ratio) were assessed through an experimental Box‐Behnken design (four variables and three levels). Results indicated a variation from 3.74 to 0.03 mg GAE/g of extract (total polyphenol), 7.77 to 0.5 mg/L (gallic acid), 0.55 to 0.27 mg/L (ellagic acid), 0.26 to 0.02 mg/L (caffeic acid), 0.86 to 0.25 mg/L (rutin) and 2.43 to 0.89 mg/L (mangiferin), and different effects were observed depending on the compounds. In summary, MAE may be used as a suitable approach for the selective extraction of total polyphenols from Physalis angulata. Practical Applications Microwave‐assisted extraction (MAE) is a potential technique to obtain total phenolic compounds from vegetable sources. This approach increases the yields and reduces the extraction time and the consumption of solvent compared with traditional extraction methods. Extract from Physalis angulata shows high polyphenol content and ethnopharmacological value which may be applied as preservative (in food industry) or due to its biological properties (antioxidant, antipyretic, analgesic and anti‐inflammatory).
Article
Sixteen new withanolides, physangulatins A-N (1-14) and withaphysalins Y and Z (15 and 16), as well as 12 known analogues, were isolated from the stems and leaves of Physalis angulata L. Their structures were established using extensive spectroscopic data analyses. The absolute configurations of 1 and 9 were assigned via X-ray crystallography. The isolated compounds were tested for their antiproliferative effects against human prostate cancer cells (C4-2B and 22Rvl), human renal carcinoma cells (786-O, A-498, and ACHN), and human melanoma cells (A375-S2), as well as inhibitory effects on NO production induced by LPS in macrophages. Compounds 9, 17, 20, 21, 25, and 27 showed antiproliferative effects against all tested cancer cells, with IC50 values of 0.18-7.43 μM. Compounds 3-5, 9-11, 17, 20-22, 24, 25, and 27 displayed inhibitory effects against NO production, with IC50 values of 1.36-11.59 μM.
Article
A new phenyldihydronaphthalene-type lignan, (3R,4S)-6-hydroxy-4-(4-hydroxy- 3-methoxyphenyl)-5,7-dimethoxy-3,4-dihydro-2-naphthaldehyde-3a-O-β-d-glucopyranoside (1), and a new phenylnaphthalene-type lignan, 6,7,4'-trihydroxy-3'-methoxy-2,3- cycloligna-1,4-dien-2a,3a-olide (2), along with 10-known lignan derivatives (3-12) were isolated from the aerial part of Vitex negundo var. heterophylla. Their structures were established by comprehensive 1D- and 2D-NMR spectroscopic analyses.
Article
Human T-lymphotropic virus type 1 (HTLV-1) induces a strong activation of the immune system, especially in individuals with HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Physalin F is a secosteroid with potent anti-inflammatory and immunomodulatory activities. The present study aimed to investigate the effects of physalin F on peripheral blood mononuclear cells (PBMC) of HAM/TSP subjects. A concentration-dependent inhibition of spontaneous proliferation of PBMC from HAM/TSP subjects was observed in the presence of physalin F, as evaluated by 3H-thymidine uptake. The IC50 for physalin F was 0.97 ± 0.11 μM. Flow cytometry analysis using Cytometric Bead Array (CBA) showed that physalin F (10 μM) significantly reduced the levels of IL-2, IL-6, IL-10, TNF-α and IFN-γ, but not IL-17A, in supernatants of PBMC cultures. Next, apoptosis induction was addressed by using flow cytometry to evaluate annexin V expression. Treatment with physalin F (10 μM) increased the apoptotic population of PBMC in HAM/TSP subjects. Transmission electron microscopy analysis of PBMC showed that physalin F induced ultrastructural changes, such as pyknotic nuclei, damaged mitochondria, enhanced autophagic vacuole formation, and the presence of myelin-like figures. In conclusion, physalin F induces apoptosis of PBMC, decreasing the spontaneous proliferation and cytokine production caused by HTLV-1 infection.
Article
Leishmaniasis are a neglected group of emerging diseases that have been found in 98 countries and are caused by protozoa of the genus Leishmania. The therapy for leishmaniasis causes several side effects and leads to drug-resistant strains. Natural products from plants have exhibited activities against Leishmania in various experimental models. Physalis angulata is a widely used plant in popular medicine, and in the literature it has well-documented leishmanicidal activity. However, its mechanism of action is still unknown. Thus, this study aims to evaluate the mechanism driving the leishmanicidal activity of an aqueous extract of Physalis angulata root (AEPa). AEPa was effective against both promastigotes and intracellular amastigote forms of L. amazonensis. This effect was mediated by an increase of reactive oxygen species (ROS), but not of nitric oxide (NO). The increased production of ROS induces cell death by phenotypes seems by apoptosis cell death in Leishmania, but not autophagy or necrosis. In addition, morphological analysis of macrophages showed that AEPa induced a high number of cytoplasmic projections, increased the volume of cytoplasm and number of vacuoles, caused cytoskeleton alterations and resulted in high spreading ability. AEPa also promoted superoxide anion (O2−) production in both uninfected macrophages and those infected with Leishmania. Therefore, these results revealed that AEPa causes cell death by phenotypes seems by apoptosis cell death in L. amazonensis and modulates macrophage activation through morphofunctional alterations and O2− generation to induce Leishmania death.
Article
Physalis angulata is an annual herb widely used in popular medicine for the treatment of a variety of pathologies. This review shows research over the last 30 years, about traditional uses, chemical constituents and pharmacology of this specie. The studies related to traditional uses show that P. angulata is known for its antimalarial, anti-inflammatory and post-partum treating properties. It presents the different pharmacological experiments in vitro and in vivo models that have been made, also the identification of phytochemical constituents with medicinal importance, the main being physalins and withanolides. Pharmacological studies have shown antiparasitic, anti-inflammatory, antimicrobial, antinociceptive, antimalarial, antileishman-ial, immunosuppressive, antiasthmatic diuretic, and antitumor activities, thus validating its traditional uses and demonstrating the great potential of this specie for further development within the pharmaceutical industry.
Article
Introduction: The Annonaceae family is known as a promising abundant source of secondary metabolites, especially annonaceous acetogenins, terpenoids and isoquinoline-derived alkaloids. Although widely investigated from the phytochemical viewpoint, this family still presents some largely unexplored genera, e.g. the Bocageopsis. Objective: To investigate the alkaloid content of Bocageopsis pleiosperma Maas using direct infusion electrospray ionisation ion trap tandem mass spectrometry (ESI-IT-MSn) analysis. Methodology: Dichloromethane extracts of aerial parts were subjected to acid–base partitioning to yield the alkaloidal fractions. These fractions were analysed by direct infusion into a (+)ESI-IT-MSn system. The alkaloidal fraction from the leaves was also obtained on a large scale and subjected to chromatographic separation. Results: The tentative MSn-based identification of alkaloids in leaves, twigs and trunk bark showed that aporphine alkaloids were restricted to the leaves and twigs, tetrahydroprotoberberine alkaloids were only found in the twigs and trunk bark while benzylisoquinoline alkaloids were found in the leaves, twigs and trunk bark. Chromatographic separation of the leaf alkaloidal fraction yielded the aporphine alkaloids nornuciferine, asimilobine and isoboldine, the β-carboline alkaloid tetrahydroharman and some mixtures containing benzylisoquinoline and aporphine alkaloids, all described for the first time in the Bocageopsis genus. Furthermore, tetrahydroharman has not previously been reported in the Magnoliales order. Conclusion: Direct infusion ESI-IT-MSn analysis of alkaloids allowed fast recognition of alkaloidal classes previously reported in the Annonaceae family, aiding the chromatographic step and allowing a selective isolation of compounds previously not identified in the Bocageopsis genus.
Article
Essential oils from the leaves, twigs and barks of Bocageopsis pleiosperma Maas were obtained by using hydrodistillation and analysed by using gas chromatography coupled to mass spectrometry. Several compounds (51) were detected and identified, being b-bisabolene the main component in all aerial parts of the plant, with higher concentration in the leaves (55.77%), followed by barks (38.53%) and twigs (34.37%). In order to increase the biological knowledge about the essential oil of Bocageopsis species, antimicrobial activities were evaluated against the microorganisms Escherichia coli, Staphylococcus epidermidis, Enterobacter aerogenes, Candida tropicalis, Candida dubliniensis, Candida glabrata and Candida albicans. The essential oil obtained from the barks exhibited a moderate effect against S. epidermidis ATCC 1228 (MIC = 250 mg/mL), while the other oils did not exhibit antimicrobial activity. These results represent the first report about the chemical composition of B. pleiosperma and the first antimicrobial evaluation with a Bocageopsis species.
Article
One new flavonol methyl ether (1), along with four known compounds from the leaves of methanol extract of Vitex peduncularis Wall and three known compounds from the leaves of methanol extract of Vitex pinnata Linn (Verbenaceae) were isolated. The chemical structure of the new compound was established by detailed spectroscopic studies. The in vitro antileishmanial activities of 1 against both Leishmania donovani promastigote and amastigote forms were evaluated. To characterize the effector mechanism of compound 1 against Leishmania parasite infected THP-1 macrophage cells, RT-PCR analysis of inducible nitric oxide synthase 2 (iNOS2) was done followed by measurement of nitric oxide generation by Griess reaction. Pentostam (sodium antimonygluconate) was used as reference drug. Compound 1 exhibited better antileishmanial activity than sodium antimonygluconate (SAG) (having IC50 values for promastigote, 2.4 and 58.5 μM and for amastigotes, 0.93 and 36.2 μM, respectively). Compound 1 was less toxic than SAG towards THP-1 having CC50 of 123.7 μM and 364.3 μM, respectively. Moreover, compound 1 was found to induce a potent host-protective response by enhancing NO generation and iNOS2 expression in infected macrophages to prevent the progression of Leishmania parasite.
Article
The 95% ethanol extract of the whole plant of Physalis angulata Linn. afforded one new skeletal physalin named aminophysalin A (1) and one new naturally occurring 5β-hydroxy-6a-chloro-5,6-dihydrophysalin B (2), together with five known physalins (3-7). Their structures were elucidated through MS, IR, NMR spectroscopy analyses and X-ray crystallography. Aminophysalin A (1) had an absolutely unusual structural feature in the chemistry of physalins with a nitrogen atom. Compounds 1-7 were evaluated for quinone reductase activities in hepa 1c1c7 cells. Physalin H (6) showed strong quinone reductase induction activity with IR (Induction ratio, QR induction activity) value of 3.74±0.02, using 4-bromoflavone as a positive control substance (2.17±0.01, 10 μg/mL), while compounds 1, 2, 3, 5 showed weak quinone reductase induction activity.
Article
Six new diterpenoids, 4-epi-7α-O-acetylscoparic acid A (1), 7α-hydroxyscopadiol (2), 7α-O-acetyl-8,17β-epoxyscoparic acid A (3), neo-dulcinol (4), dulcinodal-13-one (5), and 4-epi-7α-hydroxydulcinodal-13-one (6), and a new flavonoid, dillenetin 3-O-(6″-O-p-coumaroyl)-β-d-glucopyranoside (10), along with 12 known compounds, were isolated from the aerial parts of Scoparia dulcis. The 7S absolute configuration of the new diterpenoids 1-4 and 6 was deduced by comparing their NOESY spectra with that of a known compound, (7S)-4-epi-7-hydroxyscoparic acid A (7), which was determined by the modified Mosher's method. The flavonoids scutellarein (11), hispidulin (12), apigenin (15), and luteolin (16) and the terpenoids 4-epi-scopadulcic acid B (9) and betulinic acid (19) showed more potent α-glucosidase inhibitory effects (with IC50 values in the range 13.7-132.5 μM) than the positive control, acarbose. In addition, compounds 1, 11, 12, 15, 16, and acerosin (17) exhibited peroxisome proliferator-activated receptor gamma (PPAR-γ) agonistic activity, with EC50 values ranging from 0.9 to 24.9 μM.
Article
This article describes, for the first time, the chemical constituents of the essential oils from fresh leaves of Bocageopsis multiflora, collected in two seasons, and some of its biological activities. The oils were analyzed by gas chromatography–flame ionization detector (GC–FID) and gas chromatography–mass spectrometry (MS) and showed a high proportion of sesquiterpenes. The main constituent of the oil collected in the rainy season was bisabolene (13.2%), while the main constituent in the dry season was spathulenol (16.2%). The highest yield (0.3%) was obtained for the oil collected in the rainy season, which was assayed against Leishmania amazonensis promastigote forms, exhibiting significant activity (IC50 of 14.6 μg/mL). Comparison between the oil and the reference drug (pentamidine isethionate) showed non-toxic effects for mice peritoneal macrophages treated at IC50 of each sample. The results obtained in the prothrombin time and activated partial thromboplastin time tests indicated that the oil acted as a procoagulant, causing activation of coagulation in both pathways.
Article
Five new bidesmosidic saponins (1–5), along with six known triterpenoid saponins, were isolated from the methanolic extracts of the leaves and twigs of Abuta grandifolia. The ethyl acetate extracts allowed the isolation of three tropoloisoquinolines and of one isoquinoline; all were known alkaloids. The structures of all compounds were elucidated on the basis of extensive spectroscopic data analysis.
Article
A new limonoid, cedrelanolide I (1), has been isolated from the stem bark of Cedrela salvadorensis (Meliaceae). The structure was established by spectroscopic methods and X-ray diffraction analysis.
Article
Two varieties of Cedrela toona Roxb. are available in West Bengal and the seeds of one variety produces cedrelone, 1,2-dihydrocedrelone, bergapten and β-sitosterol. Occurrence of 1,2-dihydrocedrelone, a new tetranortriterpenoid, provides further interesting evidence of the chemotaxonomic feature of Meliaceae.
Article
The methanol extract of the aerial part of Tessaria integrifolia (common name: pajaro bobo), which is used as an herb for the treatment of asthma and liver injury in Peru, showed a stronger antioxidative activity than the standard synthetic antioxidant, 3-tert-butyl-4-hydroxyanisole (BHA). From this extract, five new eudesmane-type sesquiterpenoids were isolated along with eighteen known compounds, and their structures were elucidated on the basis of MS, 1H-NMR and 13C-NMR data. Among them, eleven phenolic compounds, four flavonoids, two lignans and five caffeoyl quinic acid derivatives were examined for their antioxidative activity using the ferric thiocyanate method, and nine compounds indicated a stronger antioxidative activity than the standard natural antioxidant, α-tocopherol at a concentrataion of 0.5 mM. Especially, two flavonoids were identified as stronger antioxidants than BHA. The scavenging effect of the phenolic compounds on the stable radical 1,1-diphenyl-2-picrylhydrazyl was examined. All tested compounds showed this scavenging effect, with the effect of five caffeoyl quinic acid derivatives and three flavonoids being almost twice or more that of α-tocopherol at a concentration of 0.01 mM.
Article
From the ethanolic extract of the heartwood of Cedrela odorata were isolated gedunin, 3β-O-β-d-glucopyranosyl-24-methyllenecholesterol, oleanonic acid, sitosterol, n-octacosanol and a new triterpene threo-23,24,25-trihydroxytirucall-7-en-3-one. Structural determinations of these compounds were made by spectrometric data. GC-MS analysis of the essential oil identified the sesquiterpenoids α-copaene, β-elemene, α-muurolene, calamenene, guayazulene, dihydroguayazulene, torreyol, γ-muurolene and α-cubebene.
Article
The co-occurrence of mexicanolide and 3-β-hydroxy-isomexicanolide in the seeds of Cedrela fissilis Velloso is recorded.
Article
Aerial parts of 23 species distributed in 10 genera of the Amaranthaceae have been examined for the presence of betaines. Glycinebetaine was isolated from all the species studied and, in addition, trigonelline was detected in eight out of the nine species of Amaranthus, 1 of the two species of Alternanthera and in the species of Iresine (3), Celosia (2), Chamissoa (1), Aerva (1), Gomphrena (1) and Froelichia (1). With the exception of I. herbstii, glycinebetaine was the predominant betaine. The highest yield of this compound was from Cyathula geniculata (2.11%, dry weight), but, with the exception of I. herbstii (0.05%), the species tested had contents in the range 0.28–2.11%, dry weight. Trigonelline yields varied from 0.004 to 0.15%, dry weight. From the data obtained, classification of the Amaranthaceae as a betaine – accumulating family would appear to be justified.
Article
Twenty-three new triterpenoids (1–23), all having an apotirucallane skeleton, were isolated from the seeds, leaves, and stems of Cedrela sinensis (Meliaceae). Their structures were determined by 2D NMR experiments, X-ray crystallographic analysis, and chemical methods. These triterpenoids showed a moderate cytotoxic activity against P-388 murine leukemia cells (IC50 0.26–9.9μg/mL).
Article
Bond dissociation enthalpies (BDEs) for phenolic constituents from Tessaria integrifolia Ruiz. et Pavon and Piper elongatum VAHL. have been calculated using the semi-empirical molecular orbital (MO) method (PM3). A significant correlation between the BDE of the phenolics and their radical-scavenging effect was found. The BDEs evaluated by semi-empirical MOs can provide a convenient and useful clue for assessment of the antioxidative activity of phenolics.
Article
In a survey of the higher plants for families with rosmarinic acid-accumulating species we could show for the first time, that some species of the family Marantaceae of the order Zingiberales accumulate rosmarinic acid. Other compounds detected in Marantaceae are chlorogenic acid and rutin (quercetin 3-O-rutinoside). Out of 35 species coming from 9 different genera extracted and analysed, two species of Maranta (Maranta leuconeura, Maranta depressa) and one Thalia species (Thalia geniculata) showed the presence of rosmarinic acid. The two Maranta species additionally contained chlorogenic acid, which was also present in Stromanthe amabilis. Rutin was detected in the genera Calathea, Ctenanthe, Maranta, Pleiostachya and Thalia. For a comparison, species from six other families of the Zingiberales were analysed as well.
Article
Recently, our group isolated and reported the antiproliferative activity in promastigotes and axenic amastigote forms of Leishmania amazonensis treated with 5-methyl-2,2':5',2″-terthiophene (compound A) and 5'-methyl-[5-(4-acetoxy-1-butynyl)]-2,2'-bi-thiophene (compound B) isolated from the aerial parts of Porophyllum ruderale. Here, we demonstrated that both compounds exhibited activity against intracellular amastigotes showing IC50 values of 37 and 51 µg/mL for compounds A and B, respectively. Both compounds showed low levels of toxicity for human cells, even at the highest concentrations (hemolytic index < 10 % at 500 µg/mL). Promastigotes treated with compound A showed an alteration in the mitochondrial membrane when observed by flow cytometry through labeling with rhodamine 123 and this was confirmed by transmission electron microscopy. Alterations on morphology (rounded cells) were observed by scanning electron microscopy in parasites treated with the compounds. Further studies should be performed employing compounds A and B for the development of new drugs for chemotherapy of leishmaniasis.